Personalised dosing of certolizumab pegol based on serum concentration in rheumatoid arthritis

Rheumatoid arthritis is a chronic disease where the patient’s own immune system induces painful and destructive inflammation in the joints of the hands and feet. Rheumatoid arthritis is a limiting, potentially disabling disease to patients, and is associated with significant costs to society, both related to treatment and disability. In the last two decades, drugs that reduce the activity of the immune system have revolutionized the treatment of rheumatoid arthritis. Tumor necrosis factor (TNF) inhibitors, is a class of drugs that suppress tumor necrosis factor (TNF), a substance in your body that causes inflammation. Certolizumab pegol is one of five TNF inhibitors in common use.

With modern treatment such as TNF inhibitors, low disease activity or even remission is realistic in patients with rheumatoid arthritis. However, all TNF inhibitors are expensive treatments and not all patients respond adequately. One way to improve treatment effect of TNF inhibitors is to personalize treatment based on each patient’s drug level in blood. If the drug level is low, the patient increases the drug dose, and if the drug level is high, the patient reduces the drug dose. This strategy, where we aim for a predefined therapeutic drug concentration interval, is called therapeutic drug monitoring, TDM. Personalised dosing based on TDM may improve treatment effect and cost-effectiveness in patients treated with TNF inhibitors. This was shown in the randomised clinical Norwegian Drug Monitoring (NOR-DRUM) trials, conducted by our research group. The trials showed that TDM leads to better outcomes in the maintenance phase of treatment with the TNF inhibitor infliximab in patients with immune-mediated inflammatory diseases, including patients with rheumatoid arthritis. Infliximab is the only TNF inhibitor administered intravenously in a hospital setting. We do not know if TDM also improves outcomes in patients treated with other TNF inhibitors (such as certolizumab pegol), which are administered by the injection of the drug by a syringe or autoinjector into the fatty layer of tissue under the skin, by the patients themselves.

We are planning a clinical trial to investigate the possible benefit of TDM of TNF inhibitors administered by injection under the skin in rheumatoid arthritis. Certolizumab pegol will be included in the trial. Before we can conduct the trial, we need to know which certolizumab pegol serum levels to aim for, and how changes in dosing affects serum levels. Access to data from existing trials will help establish this. The impact of certolizumab pegol dose and a range of covariates (i.e. independent variables that can influence the outcome of a given statistical trial, but which are not of direct interest) on serum certolizumab pegol levels will be assessed by comparing mean/median and change in certolizumab pegol levels between groups and by statistical methods which allow more complex comparisons.

By optimising treatment with TNF inhibitors by personalised dosing, the proposed research has potential to improve treatment and quality of life for a large group of patients with rheumatoid arthritis. This project is part of the SQUEEZE project, which is a European research consortium investigating personalised medicine for rheumatoid arthritis. SQUEEZE is funded by the European Union (Horizon 2022), https://squeeze-project.eu/